Recent advances in our knowledge of thyroid pathology have indicated that the clinical presentation of many thyroid abnormalities is dependent on the relative preponderance of thyroid-stimulating and/or thyroid destructing antibodies which result in a spectrum of disease from hyper- to hypothyroidism. The mechanisms responsible for the development of these organ specific antibodies are, however, ill understood. We propose therefore, to investigate the immunological defects in autoimmune thyroid disease by developing and utilizing hemolytic plaque-forming cell (PFC) assays for the detection of immunocytes secreting IgG and specific antibodies to a variety of thyroid antigens. In PFC assays based on Protein-A coated sheep red blood cells (SRBC) we shall quantitate circulating and intra-thyroidal IgG secreting lymphocytes in Graves' and Hashimoto's disease and manipulate the T:B cell ratios to sensitively investigate B-cell function in-vitro with and without mitogenic stimulation. With the use of thyroglobulin and thyroid cell membrane-fraction coated SRBC we shall compare total IgG secretion with specific antibody production and regulation. These techniques will enable us to assess, both in-vivo and in-vitro, the influence of anti-thyroid therapy (drugs, surgery and irradiation) on immunological mechanisms in this disease spectrum. Such investigations will lead to studies of families with autoimmune thyroid disease in an attempt to localize immune abnormalities in children and young people with a high probability of developing thyroid dysfunction.